EP0052770A1 - Rotor muni de segments amovibles pour analyseur centrifuge - Google Patents
Rotor muni de segments amovibles pour analyseur centrifuge Download PDFInfo
- Publication number
- EP0052770A1 EP0052770A1 EP81108752A EP81108752A EP0052770A1 EP 0052770 A1 EP0052770 A1 EP 0052770A1 EP 81108752 A EP81108752 A EP 81108752A EP 81108752 A EP81108752 A EP 81108752A EP 0052770 A1 EP0052770 A1 EP 0052770A1
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- European Patent Office
- Prior art keywords
- rotor
- sample
- elements
- insert
- analysis
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/40—Static mixers
- B01F25/42—Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
- B01F25/43—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
- B01F25/432—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction with means for dividing the material flow into separate sub-flows and for repositioning and recombining these sub-flows; Cross-mixing, e.g. conducting the outer layer of the material nearer to the axis of the tube or vice-versa
- B01F25/4321—Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction with means for dividing the material flow into separate sub-flows and for repositioning and recombining these sub-flows; Cross-mixing, e.g. conducting the outer layer of the material nearer to the axis of the tube or vice-versa the subflows consisting of at least two flat layers which are recombined, e.g. using means having restriction or expansion zones
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/40—Static mixers
- B01F25/45—Mixers in which the materials to be mixed are pressed together through orifices or interstitial spaces, e.g. between beads
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/40—Static mixers
- B01F25/45—Mixers in which the materials to be mixed are pressed together through orifices or interstitial spaces, e.g. between beads
- B01F25/452—Mixers in which the materials to be mixed are pressed together through orifices or interstitial spaces, e.g. between beads characterised by elements provided with orifices or interstitial spaces
- B01F25/4523—Mixers in which the materials to be mixed are pressed together through orifices or interstitial spaces, e.g. between beads characterised by elements provided with orifices or interstitial spaces the components being pressed through sieves, screens or meshes which obstruct the whole diameter of the tube
- B01F25/45231—Mixers in which the materials to be mixed are pressed together through orifices or interstitial spaces, e.g. between beads characterised by elements provided with orifices or interstitial spaces the components being pressed through sieves, screens or meshes which obstruct the whole diameter of the tube the sieves, screens or meshes being cylinders or cones which obstruct the whole diameter of the tube, the flow changing from axial in radial and again in axial
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/71—Feed mechanisms
- B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
- B01F35/71725—Feed mechanisms characterised by the means for feeding the components to the mixer using centrifugal forces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
- B04B—CENTRIFUGES
- B04B5/00—Other centrifuges
- B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
- B04B5/0407—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers for liquids contained in receptacles
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N21/07—Centrifugal type cuvettes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/028—Modular arrangements
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/16—Reagents, handling or storing thereof
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/02—Identification, exchange or storage of information
- B01L2300/021—Identification, e.g. bar codes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0803—Disc shape
- B01L2300/0806—Standardised forms, e.g. compact disc [CD] format
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
Definitions
- the present invention relates to a rotor unit for a centrifugal analyzer with a rotor base connected to a drive and a rotor head connected in operation to the rotor base, which chambers for receiving a sample liquid and radially outward from the respectively assigned test chambers, measuring chambers for measuring for the detection of Components of the sample include characteristic parameters and fluid channels for connecting the sample chambers and the measuring chambers.
- the invention further relates to insert elements and a centrifugal analyzer which are adapted for use with the rotor unit according to the invention.
- Centrifugal analyzers with a rotor unit of the type described in the introduction have been in use for a number of years for the purposes of chemical analysis, in particular in clinical chemistry. They have a circularly symmetrical rotor unit. s with a plurality of radially extending analysis channels. From the inside to the outside, each analysis channel usually has a trough-shaped reagent chamber, a sample chamber and a measuring chamber, which in the known devices is designed as an optical cuvette.
- the rotor unit can be divided into a rotor base and a rotor head mounted on the rotor base in a rotationally fixed manner.
- the rotor base is usually designed as a plate or frame and firmly connected to the axis of the rotor drive.
- the term rotor head denotes the remaining part of the rotor unit, which in particular includes the analysis channels mentioned. With newer centrifugal analyzers the rotor head is as Exchangeable unit and is rotatably connected to the rotor base during operation.
- the rotor head and the rotor base can each be configured very differently and in particular also differ significantly in the diameter of their outer boundary.
- the rotor base can only consist of a holder for the rotor head which is integrally connected to the rotor drive axis and which is completely overlaid by the rotor head during operation.
- the rotor head is filled with reagents and samples in the known devices in the state.
- a device that can be used for this is described in DE-AS 26 26 810, which also relates to the construction of a typical rotor. is removed. As can be seen from this document, a complicated mechanical device is necessary for the automatic filling of the rotor.
- the known rotor heads are inserted into the centrifugal analyzer and connected to the rotor base.
- the rotor is rotated rapidly, with some such devices using alternating speeds for mixing. Due to the centrifugal acceleration when the rotor rotates, the reagent is conveyed from its chamber into the sample chamber and then both together into the measuring chamber. It is then measured there with the rotor running.
- this measurement consists of a determination of the optical density of the liquid in the measuring chambers designed as optical cuvettes. Thanks to modern electronic evaluation devices, the absorption in each cuvette can be measured with every rotor revolution. As a result, the absorption in all cuvettes can be observed almost continuously. At a typical rotation speed of 1000 revolutions per minute, 1000 measurements are carried out per minute for each cuvette.
- This method results in an accuracy of the measurement that can hardly be achieved with conventional analysis devices at a comparable analysis frequency, in particular in so-called kinetic analysis determinations in which the speed of the reaction course provides information about the concentration of a specific component of the sample.
- centrifugal analyzers have a number of significant advantages, but also significant disadvantages.
- a summary of the most important requirements for an optimal analysis device can already be found in one of the first publications on centrifugal analyzers, namely the article by Norman G. Anderson in "Analytical Biochemistry", volume 28, pages 545-562 from 1969.
- One of these requirements is the practically simultaneous measurement of several reactions, which, as described above, enables better monitoring of the individual reaction processes.
- Another requirement is that the volumes of the reagents and samples should be as small as possible. This requirement is largely met by the known centrifugal analyzers, but an improvement is still desirable.
- Centrifugal analyzers also allow easy connection to modern data processing systems to evaluate the measurement results, i.e. both for converting the absorption values into the desired concentration data and for statistical evaluation of these concentrations in order to be able to provide the doctor with as much information as possible.
- the known rotors are in particular only suitable for carrying out an analytical determination for a large number of samples in one rotor run.
- a number of different analytical determinations must be carried out in a clinical laboratory, for example on the blood of a patient, which are also referred to as a profile.
- this requires considerable organizational effort, because the individual analytical determinations, for example those communicated to the clinical laboratory by the doctor on a request card, have to be carried out gradually in separate rotor runs on one or more centrifugal analyzers. Then the separately determined data are summarized and communicated to the doctor.
- This complicated procedure not only requires a great deal of organizational effort, but is unfortunately always the cause of communication errors, which may then result in incorrect therapeutic measures by the doctor.
- centrifugal analyzers which can be adapted to various tasks in a more variable and flexible manner and in particular to the profile analyzes or at least suitable for several different analytical determinations in one rotor run. This is particularly important for emergency analysis, where several different analytical determinations for a sample, ie for a patient, may have to be carried out in the shortest possible time.
- sampling i.e. in particular the collection of serum or plasma from the blood and sample preparation, i.e. in particular, the dilution of serum or plasma to the concentrations required for the analysis are carried out in separate work steps outside the analyzer. It is immediately obvious that additional manual work steps and in particular transfer operations are necessary. These in turn can lead to confusion or, for example, contamination of the sample.
- the object of the present invention is to design a rotor unit for a centrifugal analyzer of the type described at the outset in such a way that, while avoiding the disadvantages of known centrifugal analyzers, it enables the simplest possible operation and the most flexible and versatile use of the device.
- the invention is intended to provide insert elements for use in a rotor unit according to the invention and a correspondingly designed centrifugal analyzer.
- the invention proposes to design a rotor unit of the type mentioned at the outset in such a way that the rotor head includes a plurality of different insert elements which are interchangeable and can be connected to the rotor base at various locations, in a positionally stable manner during operation.
- Each insert element contains facilities for carrying out sub-steps of analytical determinations.
- the outer elements of the insert elements can be different, but they can differ, for example, only in the chemical composition of a part of their components. It is essential that the proposal according to the invention, instead of using the hitherto customary, uniformly constructed rotors whose rotor head can accommodate a plurality of different insert elements, achieves a substantially increased variability.
- each insert element can be optimally adapted for a specific task. Due to the possibility of connecting a plurality of different insert elements to the rotor base, an individually adapted rotor can be put together for each rotor run, which rotor can then be used in a much more varied manner. For example, this makes it easy to determine several components of a sample (profile determinations) in one rotor run. In addition, there are considerable simplifications in handling, as will be shown below.
- analysis elements of different designs can be used as insert elements. These include single analysis elements, which include devices for determining one component of the sample, and also multiple analysis elements, which have devices for the simultaneous determination of several components of one or more samples.
- insert elements can now be completely tailored to the respective analysis task. They can include in their shape different Anal y sekanäle, which are fed with liquid reagents. However, they can also contain prepackaged reagents, in particular in solid form, which, as will be explained later, are then dissolved and mixed with the diluted sample.
- the term "insert element” or “analysis element” includes any shape and size. Particularly simple Anal y soul elements may be impregnated with reagents papers or nonwovens that can be interchangeably used in the rotor head, for example.
- the insert elements which can be connected to the rotor base according to the invention include elements for obtaining and preparing the samples. These measures also eliminate a major disadvantage of known centrifugal analyzers. So far, the sample has been obtained and prepared independently of the analyzer. In the case of blood analysis, the blood had to be centrifuged to obtain serum or plasma, for example, and then diluted accordingly before it could be fed to the test chambers of a centrifugal analyzer. As mentioned above, complicated apparatus was used to transfer the samples into the rotor head outside the device, or pipetting had to be carried out by hand.
- the spatial dimensions of the insert elements preferably complement one another in such a way that larger elements can be connected to the rotor base at the location of an integer majority of the smallest elements. You can also express this proposal according to the invention so that the dimensions of the insert elements adhere to a grid dimension. A certain integer fraction of the rotor area or the rotor circumference determines the basic unit of the grid. The individual insert elements are then designed so that their space requirement corresponds to a multiple of this basic grid unit. This measure makes the rotor unit according to the invention particularly variable because larger insert elements can now take up the space of several smaller insert elements without wasting space.
- the holders for the insert elements are preferably arranged periodically on the rotor base for the same reason, insofar as they are each on the same circumference, the periodicity length of the holder arrangement corresponding to the basic unit of the grid.
- the invention is not limited to the case that the insert elements are all approximately at the same radial distance from the center of the rotor. Rather, it can make sense for certain purposes to arrange the insert elements on different circumferences of the rotor, for example in order to allow different centrifugal accelerations to act on the different elements at the same speed. In this case, the holders for the insert elements will also have a different radial distance from the rotor center, i.e. they lie on different circumferences.
- a circular sector-shaped design of the insert elements when viewed from the top of the rotor is particularly preferred because this means that different insert elements connect seamlessly to one another and the unity of the insert elements results in an uninterrupted surface of the rotor head when the rotor is completely included Insert elements is loaded, but this is not necessary.
- the term "circular sector-shaped" is to be understood here in such a way that the boundary lines of the sectors, that is to say when the rotor is viewed from above, the boundary lines of the insert elements essentially extend along radii of the rotor circle.
- the inventive proposal includes solutions in which the outer edges deviate from the course of these radii in a certain manner, which is repeated in the different elements, so that the various insert elements, even though they have no straight side faces, become uninterruptedly occupied complement the rotor base.
- Such a design can be particularly advantageous in order to hold the insert elements together by form-fitting design of their side surfaces.
- the rotor head in two parts, namely in a ring on the periphery of the rotor head, which contains the cuvettes for optical measurement, and an inner part which is circular in supervision and which fits precisely into the cuvette ring and has through openings on its periphery which, when assembled, align with the inlet openings of the cuvettes and seal them.
- the analysis liquid then passes from the analysis channels in the circular inner part into the cuvettes of the cuvette ring.
- Such a construction has the advantage that the cuvette ring can be made of high quality materials and very carefully, so that the cuvettes have very good optical properties, while the circular inner part can be made relatively simple.
- the invention is also designed accordingly in a preferred embodiment.
- the cuvette ring is to be regarded as part of the rotor head and is connected to the rotor base in a fixed or replaceable manner.
- All measuring chambers are preferably located on a circumference of the rotor head, i.e. they have the same radial distance from its center, so that a single evaluation unit is sufficient to determine the characteristic parameters that have to be measured to detect constituents of the sample.
- the optical absorption at one or more wavelengths is determined in the known centrifugal analyzers and preferably also in the device according to the invention as parameters characteristic for the detection of constituents of the sample.
- the invention is not limited to such optical measurements.
- the novel variability of the device according to the invention can make it possible to carry out completely different determinations in a centrifugal analyzer. These include, for example, electrical measurements in connection with various types of electrochemical analysis methods.
- the measuring chambers have electrodes, the signals of which are supplied to the evaluation device of the device in a suitable manner, for example via sliding contacts or wirelessly.
- the measuring chambers can also lie on different circumferences of the rotor head,
- the sample collection and / or sample preparation elements have sampling points at which samples can be taken using suitable devices of the device, for example cannulas of automatic metering devices, so-called dispensers or dilutors. These removal points are preferably located on a circle with the same radius as the feed openings of the sample chambers of the analysis elements. This makes it possible for the overpass to use the samples from the sample collection or sample preparation elements to the analysis elements dosing devices that only move in the vertical direction.
- the rotor is then brought into the position suitable for a removal or feed process by a step switching device integrated in the drive.
- the insert elements have codes relating to the sample and / or the components of the sample to be determined with the respective element. These codes can be read by a reading device built into the centrifugal analyzer in order to inform the device of essential data for the evaluation and at the same time to obtain control by the operating personnel for the correct loading of the rotor with insert elements.
- the insert elements preferably have marks for triggering the measuring process. The position of the insert elements in relation to the rotor base naturally has certain tolerances, even if the holder is carefully designed. Since the measuring process generally has to be triggered with reference to the position of the insert element, it is particularly advantageous if the relevant marks are located on the insert element and not on the rotor base.
- the mounting parts which are preferably used by positive engagement with the insert elements for their precise mounting on the rotor base, are preferably arranged in the vicinity of the measuring cells. This means that any tolerances in the dimensions of the insert elements with regard to the positioning of the measuring cells have little effect.
- the present invention also includes insert elements for use with a rotor unit according to the invention, which are particularly adapted to this purpose and enable further preferred embodiments of the rotor unit according to the invention.
- Preferred insert elements of this type include the reagents for carrying out analytical determinations in a form which can be stored and transported with the insert element.
- Such analysis insert elements are particularly advantageous to use as disposable elements, which are also referred to as "disposables".
- the manufacturer already supplies them with suitable reagents for certain analyzes and delivers them to the user as a unit with the reagents.
- the handling of individual, in particular liquid, reagents is thereby relieved of this, which means a considerable simplification.
- Such disposables can be produced in a large number of versions, each version being suitable for one or more identical or different analysis methods and including the corresponding reagents, but also correspondingly shaped fluid channels and other devices.
- the user then only has to select the suitable insert elements and insert them into the rotor unit according to the invention.
- a particularly preferred insert element for use in the rotor unit according to the invention contains at least one analysis reagent in dried form and a large number of very small interconnected cavities which connect the sample chamber and the measuring chamber to one another.
- Such insert elements are
- sample collection and / or preparation elements are characterized in that they are suitable for taking blood from a patient, for collecting serum or plasma under the action of centrifugal acceleration and as a sample vessel.
- These elements intended for blood analysis save two additional vessels, namely a syringe for taking blood from the patient's blood vessel and a centrifugation tube for collecting plasma or serum. At the same time, transfer processes from one vessel to another are avoided.
- it is particularly important that the extraction and preparation of the sample can take place using such insert elements in the analyzer itself and that the sample can then be taken from the sample collection and / or preparation vessel without manual steps in the Analyzer itself is transferred into the analysis elements in a simple manner.
- thermostatting the sample partial if these sample collection and / or preparation elements are used in the rotor unit according to the invention. Thermostat can namely be ensured by a suitable controlled heating of the rotor base and / or a part of the rotor head that cannot be exchanged with the insert elements, be it by a thermostated liquid flow or by direct electrical heating and cooling. In order to achieve a sufficiently precise thermostatting of the sample, it must be in thermal contact with the thermostated parts for a certain minimum time. If the sampling and sample preparation were to take place outside the rotor, then after the sample had been introduced into the rotor head connected to the rotor base, one would have to wait until the time required for thermostatting had elapsed.
- the sample in the device according to the invention is already thermostatted during the centrifuging and any further preparation steps, for example during the dilution of the sample.
- the analysis process can therefore begin shortly after the sample has been transferred to the analysis insert element.
- the resulting time saving leads to a higher analysis performance of the device, or an improved accuracy through improved thermostatting.
- the rotor unit according to the invention is preferably to be used in a specially designed centrifugal analyzer which is characterized in particular by the fact that it includes evaluation devices for determining several different components of the sample in one rotor run.
- the invention enables the determination of several different components or components of a physiological liquid in a rotor run in a simple manner.
- the determin. Mung consists of a chemical reaction and the subsequent measurement of a parameter, the value of which is characteristic of the concentration of the component to be determined.
- centrifugal analyzer used can evaluate several parameters in one rotor run. In principle, these can also be of various types, for example measurement of the optical absorption and fluorescence and, under certain circumstances, electrical values. However, a centrifugal analyzer that is suitable for determining the optical absorption at several different wavelengths in one rotor run is particularly preferred.
- polychromatic is not to be understood here as meaning that the photometer works with multicolored light. Rather, it must be a photometer that can measure at a plurality of different wavelengths, the change in wavelength being coordinated with the passage of the measuring cuvettes of the rotor in such a way that the absorption of each cuvette can be measured at any desired wavelength.
- a centrifugal analyzer adapted for use with the invention also preferably has a rotor drive which is not only suitable, as in the known devices, for driving the rotor at a speed suitable for the mixing and measuring process (usually about 1000 revolutions per minute), but also has a higher speed for centrifuging samples.
- the drive should be suitable to move the rotor step by step into certain positions, which is particularly advantageous for sample preparation and distribution.
- the rotor unit identified in its entirety by reference number 10
- the rotor unit can also be seen a rotor base 12 and a rotor head 14.
- the term “rotor head” includes all components that can be connected to the rotor base for operating the centrifugal analyzer. In particular, it includes the components necessary for the actual analysis.
- various analysis insert elements for example single analysis elements 16 and multiple analysis elements, such as the illustrated triple analysis elements 18, seven-fold analysis elements 20 and eleven-fold analysis elements 21.
- a combined sample extraction and preparation element 22 can also be seen.
- Both the rotor base 12 and the insert elements 16, 18, 20, 21 and 22 contain machine-readable codes 24 and 26, respectively.
- the analysis elements have feed openings 28 for feeding the sample in the sample chambers 29, cuvette windows 30 and bores 32, which serve as trigger marks for triggering the measuring process.
- 2 schematically shows a trigger signal generator 33 which contains a light source and an optical receiver in order to generate a trigger signal each time it passes a trigger hole.
- the beam path for the optical absorption measurement runs along the line S-S in FIG. 2 and is not shown in detail for the sake of clarity. It is of conventional design, but a polychromatic photometer is preferably used.
- an optical absorption measurement is used as a characteristic parameter for the detection of components of the sample.
- a sample reagent dispenser 34 which is also generally referred to as a dilutor and a sample distributor 36, which is generally referred to as a dispenser, are preferably used. Both are arranged to be vertically movable in the centrifugal analyzer according to the invention, as is indicated by the double arrows 38 and 40.
- the insert elements 16, 18, 20, 21 and 22 can be connected by means of holding pins 42 to the rotor base 12, which has corresponding holding grooves 43 (FIG. 2).
- the shape of the holding grooves 43 and the holding pins 42 are coordinated with one another in such a way that they cooperate in a form-fitting manner and ensure a positionally stable arrangement of the insert elements 16, 18, 20, 21 and 22.
- a central lock 44 is also provided, which can be screwed onto the rotor base 12 with a thread 46 and which is supported surfaces 48 of the insert elements 16, 18, 20, 21 and 22 rests.
- the rotor base 12 is connected to the rotor drive of the centrifugal analyzer via a drive axis 50.
- the quality of the bearing of the drive axle and the weight of the rotor base are essential for a low-vibration run of the rotor.
- the weight of the insert elements is preferably such that there is no excessive imbalance even when the rotor is loaded differently. If the rotor is not fully loaded, it may be necessary; attach appropriate weights to the rotor base to avoid excessive unbalance.
- FIG. 3 shows a top view of a centrifugal analyzer according to the invention which differs from that shown in FIGS. 1 and -2 in that it offers space for a larger number of insert elements.
- This figure is intended in particular to illustrate the advantageous rastering of the fastening according to the invention and thus the arrangement of the optionally exchangeable insert elements 16, 17, 19, 21 and 22.
- the circular area of the rotor base 12 is divided into a plurality of equally large integer fractions B.
- these fractions are sectors of the circle that are at one of the inner boundaries. 52 of the bearing surface 48 corresponding radius are cut off. Each sector corresponds to a certain angular dimension of the circle, which is referred to as the basic unit of the grid of the insert element arrangement and in the figure the reference symbol G. wearing.
- all of the holding grooves 43 for the insert elements are arranged on the same circumference H.
- the arrangement is periodic with the periodicity length a. It is essential to the invention that the periodicity length a corresponds to the basic unit G of the grid. This makes it possible to connect insert elements of different sizes, for example elements 17, 19 and 21, optionally and without wasting space at different locations on the rotor base.
- FIG. 3 In contrast to FIG. 1, analysis elements with five, eleven and seventeen analysis channels are shown in FIG. 3, which are provided with the reference symbols 17, 21 and 19.
- Elfach analysis element 21 corresponds in size to two basic units of the grid G and has two holding pins 42 on its underside.
- the seventeen-fold analysis element 1.9 has a size corresponding to three basic grid units G and three holding pins 42. It is easy to see that a particularly advantageous arrangement of different insert elements on the rotor base is possible with this construction according to the invention.
- the embodiment shown is particularly simple in so far that the insert elements per grid unit of their size each have only one holder and are designed as simple sectors with straight side edges.
- the invention includes a variety of more complicated insert element designs.
- several brackets per basic grid unit can improve the positioning of the elements.
- One of the straight. deviating the design of the side edges S4 can likewise improve the engagement from element to element and thus the accuracy of their arrangement on the rotor base 12.
- Insert elements that do not touch each other and are attached to the rotor base at a distance can also have advantages for certain applications.
- the insert elements do not all have to be arranged at the same radial distance from the center of the rotor.
- brackets are on the same circumference, but it is also advantageous in this case if the Periodicity length of the brackets located approximately on the same circumference corresponds to the basic unit of the respectively assigned insert element grid.
- the screening according to the invention can be used in a multitude of variations.
- the multiple analysis elements 17, 19 and 21 each have a number of analysis channels which is a multiple of six reduced by one.
- multiple analysis elements of the type according to the invention preferably have a number of analysis channels which corresponds to the integral multiple of a basic number reduced by one.
- the basic number is the maximum number of analysis channels of the smallest multiple analysis element + 1.
- the described preferred number of analysis channels of the multiple analysis elements results in an optimal utilization of the elements in the above-described grid division, taking into account that the side edges of the insert elements require a certain amount of space have, which corresponds approximately to the space requirement of an analysis channel.
- All cuvette windows 30 are located on a common measuring circuit, which is shown in dashed lines and provided with the reference symbol M. As a result, a single photometer is sufficient to determine all measurement results.
- the supply openings 28 of the sample chambers 29 are furthermore located in the analysis elements on the same circumference as the removal opening 56 of the combined sample collection and preparation element 22. This sample circle P is also shown in broken lines.
- the combined sample collection and preparation element 22 can be seen in cross section on the left side.
- Fig. 4 it is shown again with the associated accessories in supervision. poses. It has a preferably cylindrical interior 58, the circular cross section of the cylinder being in a plane perpendicular to the paper plane of FIG. 2.
- a piston 60 is located in the interior 58 at the left end of the insert element 22 in FIG. 4 and at the bottom in FIG .62 closed from rubber-elastic material.
- connection part 64 for a syringe needle 66 which can be connected to the insert element via a connection piece 68 which interacts with the connection part 64.
- the rear, pointed end 70 of the syringe needle 66 penetrates into the sealing plug 62 of the insert element, as a result of which an externally sealed fluid connection is established between the cavity of the needle 66 and the interior 58 of the insert element 22.
- the removal opening 56 of the combined sample collection and preparation element 22 is located in the area of the sealing plug 62. It opens into the middle of three dilution chambers 72, 74 and 76 (FIGS. 3 and 4). Similar to the connection of the syringe needle 66, the removal opening 56 is opened by a needle-like cannula 78 of the corresponding dilutor pierce and close again when the cannula 78 of the dilutor 34 is pulled out.
- a piston rod 80 can be connected, which, penetrating a bore 81, engages in a recess 82 of the piston 60 and can be non-positively connected to it.
- FIGS. 2, 5, 6 and 7. 2 shows in cross section the analysis channel of a particularly preferred analysis element. This is in the figure with the reference number 16 of a simple analysis element. Mistake. However, it should be emphasized that the design of an analysis channel described here, as well as a large number of other designs adapted to the respective analysis purpose, optionally also in a multiple. Analysis element, e.g. the elements 18, 20 and 21 can be used.
- the multiple analysis elements can also differ within an element depending on the purpose of the element, that is to say on the analytical determinations to be carried out with the element.
- the analysis element shown in cross section in FIG. 2 has a sample chamber 29, a measuring chamber 84 and a fluid channel 86 connecting them, which in the present case has a cross section which is essentially rectangular in the plane of the drawing in FIG. 2 and in the dimension perpendicular to it Drawing level has only a comparatively small clear width.
- the height of the fluid channel 86 is 6 mm, the width 1 mm.
- the capacity of the sample space 29 in this embodiment is approximately 20 ⁇ l.
- the fluid channel 86 there are nonwoven papers 88, 90 and 92, which are loaded with dried reagents suitable for the respective analysis.
- the fluid channel has a connecting channel 94 radially outward, which opens into the measuring chamber 84. This is delimited radially inwards by a barrier 96.
- the measuring chamber 84 is dimensioned such that the sample-reagent mixture fills it so far during centrifugation that the cuvette windows 30 are completely in the liquid area.
- the analysis process now takes place in principle in such a way that the sample, ie serum or plasma in the necessary dilution, is filled into the sample chamber 29 through the opening 28.
- the rotor is then brought up to speed, the sample liquid penetrating into the nonwoven papers 88, 90, 92, dissolving the reagents there and penetrating them into the measuring chamber.
- the optical absorption is determined during the centrifugation, in principle similar to known centrifugal analyzers, in order to obtain the desired concentration of a constituent of the sample. Further details are described in the cited simultaneously filed patent application by the same applicant and further below in an exemplary embodiment.
- the cuvette windows 30 must be optically transparent in the necessary spectral range. This is a particular problem, particularly at the low wavelengths used for analysis (e.g. 340 nm). Although in the illustrated embodiment the cuvette windows 30 are shown as elements inserted into an injection molded part, it may be expedient to produce a larger part or even the entire top and bottom of the analysis elements from a corresponding transparent plastic.
- the entire insert element can also consist of transparent material. Suitable optically transparent materials are e.g. Polymethyl methacrylate and polystyrene.
- the trigger bores are preferably provided in the analysis elements 16 to 21 and not, for example, in the rotor base in order to ensure a precise assignment of their position to the cuvette openings 30.
- Another advantage of this measure is that a measurement process is really only triggered at those rotor positions at which it is also necessary.
- the sample collection and preparation element 22 has an uninterrupted aperture area 35
- the single analysis element 16 has only one trigger mark
- the same-size triple analysis elements 18 and five-fold analysis elements 17 having three and five marks, respectively.
- the measuring processes would also be triggered at positions where no measurement is required at all.
- a flash lamp for the photometer of the centrifugal analyzer there is considerable energy saving and an increase in the service life if no unnecessary measurement processes and thus flashes are triggered by the triggering.
- holder of the insert elements in this case the holding pin 42, is located in the vicinity of the cuvette in the manner described at the outset. Any dimensional deviations in the manufacture of the insert elements or due to thermal expansion have only a relatively small effect on the distance of the element holder 42, 43 from the cuvette windows 30 as a result of this measure.
- the analysis elements preferably contain the reagents in a dried form that has already been prepacked by the manufacturer, because this enables particularly simple operation of the device with maximum flexibility. For special reactions, however, it can also be useful to use liquid reagents. These are preferably only filled into the analysis channel in the device. 5 shows a suitable analysis element 97 in a radial cross section through the center of its analysis channel. It can be seen that the fluid channel 86 here forms a cavity which is suitable for receiving a reagent and which is delimited by the barriers 100 and 101. A fill opening 98 for the reagent is located in the cover part 102 of the liquid analysis element 97. Sample chamber 29, fluid channel 86, Measuring chamber 84 and holding pin 42 are formed on the lower part 104 of the liquid analysis element 97, which is welded to the cover part 102.
- a corresponding reagent is applied by hand or with the help of a reagent, not shown in FIG. Circumference of the centrifugal analyzer, metering device added through opening 98.
- the subsequent analysis takes place analogously to the known centrifugal analyzers, the advantage of the device according to the invention being that liquid analysis elements 97 filled with different reagents and possibly of different designs can be used as insert elements in a rotor unit.
- FIG. 6 shows a special embodiment of an analysis channel of an analysis element 16, 17, 18, 19, .20 or 21.
- a cross section is shown approximately in the middle of the height of the nonwoven papers with the reagents according to FIG. 2. The cross section runs parallel to the rotor surface .
- the peculiarity of the embodiment shown is that radially inward adjoin the measuring chamber 84 two prechambers 106, which serve a supplementary mixture of the reagents released from the nonwoven papers 88, 90 and 92 with the sample solution.
- the centrifugal analyzer is run in a mixing run immediately before Measuring accelerated and decelerated several times, the reaction mixture alternately penetrating at least partially into the prechambers 106 and then flowing back into the measuring chamber 84 when the acceleration in the circumferential direction (tangential acceleration) stops. Very good mixing is achieved through this process.
- a mixing device based on the same principles can also have a different design than the one shown here, it being only essential that the prechamber 106 lie radially inward from the measuring chamber 84 and are connected to it via corresponding small barriers 108, the barriers being one are of such a height that they can at least partially be overcome by the liquid when the rotor is accelerating or braking and, on the other hand, do not hinder the backflow of the liquid in the absence of tangential acceleration.
- the walls 107 of the antechambers 106 are provided with a curvature which corresponds to a circle around a point in the cross section shown, which lies on the connecting line between the measuring chamber 84 and the center of the analysis rotor between these two points.
- This state of affairs is indicated in the figure by dashed auxiliary lines, the center of curvature being marked with the reference symbol K and the rotor center with the reference symbol Z.
- FIG. 7a and 7b show other devices suitable for additional mixing of the reaction mixture.
- These are static mixing devices which can be arranged in the analysis elements in the fluid channel in front of the measuring chamber 84.
- the illustration is a cross section in the plane as in FIGS. 2 and S. 'The direction of flow of the reaction mixture is indicated by arrows.
- the mixing effect is achieved in FIG. 7a by displacement bodies 110, which share the flow of the liquid and merge again to achieve a mixing effect.
- These displacement bodies can be cast in one piece on the corresponding components of the analysis element.
- a network structure 112 which is introduced into the analysis element and fastened at a corresponding point in the fluid channel 86, serves to divide the reagent mixture stream in various ways, to bring it back together and to mix it.
- a request card which can be filled in by the examining doctor, is preferably used to program the entire device. It contains a code for the sample in machine-readable form, to which the patient's name is assigned. This information is referred to as sample identification.
- sample identification a code for the sample in machine-readable form, to which the patient's name is assigned. This information is referred to as sample identification.
- requirement profile is defined by appropriate machine-readable marking, i.e. the doctor determines which components of the sample are to be determined analytically. This information is referred to below as analysis identification.
- a blood sample is taken from the patient.
- the sample identification is applied as coding 26 at the same time on the insert element 22. This can e.g. by transferring a corresponding adhesive label on the request card with bar coding to the corresponding area of the sample collection and preparation element 22.
- the device according to the invention In the clinical-chemical laboratory in which the device according to the invention is installed, the requirement cards of several patients are successively entered into a corresponding reading device of the device. In this way, the device experiences both sample identification and analysis identification. From this information, a computer built into the device determines the necessary loading of the rotor with the insert elements for the analyzes to be carried out. Appropriate 'instructions for the rotor loading are displayed on a monitor or by printer. Loading can also take place fully automatically. The loading of the rotors is carried out according to these instructions. In the embodiment of the device shown above, this is done by placing sample collection and preparation elements 22 and analysis elements 16 to 21 on the rotor base 12 in accordance with the instructions.
- the central lock 44 is closed.
- the rotor is loaded in a way that is completely tailored to the individual case. If, for example, only one analysis is required, in addition to the sample extraction and preparation element 22, only a simple analysis element 16 is attached. The next sample can then be applied. In other cases, a specific, more frequently repeated profile is requested, ie a series of analyzes that are essential for a specific clinical picture. Corresponding multiple analysis elements 18, 20, 21 can be provided for such purposes, which contain different reagents in their individual analysis channels and for which the analysis channels may also have different shapes. Such profile analysis elements allow particularly cost-effective determination of frequently recurring profiles.
- the loading of the rotor unit with the insert elements takes place outside the centrifugal analyzer.
- the unit consisting of the washer and insert elements, which in this case forms the rotor head, is then in its entirety in the Centrifugal analyzer used.
- the intermediate discs allow several rotor heads to be fitted with insert elements and thus to be prepared for the measurement, while the centrifugal analyzer, for example, is currently carrying out other analyzes.
- the sample extraction run of the rotor follows, in which the samples, i.e. the samples in the sample extraction and preparation elements. Serum or plasma can be obtained by centrifugation in the manner described above.
- sample preparation which in particular includes the corresponding dilution of the sample.
- the step switching function of the rotor drive according to the invention comes into effect.
- the rotor is brought into a position in which the dilutor 34 stands exactly above the removal opening 56 of a sample collection and preparation element 22.
- the dilutor 34 then moves vertically downward, pierces the sealing plug 62, takes the sample by suction and moves upward again in order to add differently diluted samples into the dilution chambers 72, 74 and 76 in the manner known for dilutors.
- the stepper drive brings the rotor into the correct position under the dilutor 34.
- the exact positioning of the rotor is facilitated by the codings 24 provided on the rotor base, which are read by a reading device provided on the device and in this way enable precise rotor control.
- the predilution in the dilution chambers 72, 74 and 76 has the advantage that a comparatively large amount of sample can be diluted relatively precisely. In contrast, the amount of sample transferred into the feed openings 28 of the analysis elements is very small.
- the dispenser 36 is provided to draw in a sufficient quantity of diluted samples for all analyzes to be carried out from a specific dilution of a specific sample and to distribute them into the corresponding feed openings of the sample chambers.
- the functions of the dilutor 34 and the dispenser 36 can also be performed by one unit, but the use of two separate units is advantageous in that the analysis elements are loaded more quickly.
- the rotor moves back and forth in a controlled manner by means of the codes 24 under the control of the central unit of the centrifugal analyzer.
- the dosing units 34 and 36 only have to perform vertical movements.
- the resulting mechanical simplicity of the drive that enables this movement results in an inexpensive construction and great reliability of the device.
- any liquid analysis elements 97 that may be present are charged with reagents.
- the mixing and measuring run follows, in which the centrifugal analyzer is brought up to the speeds necessary for mixing and subsequent measurement.
- the codes 26 on the insert elements 16, 18, 20, 21 and 22 read the codes 26 on the insert elements 16, 18, 20, 21 and 22 and compared them with the stored sample identification and analysis identification. If a deviation is found, an error message is given immediately. As a result, any incorrect analysis due to incorrect loading of the rotors with the insert elements is excluded with certainty. Of course, this check can also be carried out after loading before or during the sample collection run.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT81108752T ATE14797T1 (de) | 1980-11-25 | 1981-10-22 | Rotoreinheit mit einsatzelementen fuer einen zentrifugalanalysator. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19803044372 DE3044372A1 (de) | 1980-11-25 | 1980-11-25 | Rotoreinheit mit einsatzelementen fuer einen zentrifugalanalysator |
DE3044372 | 1980-11-25 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP84103637.9 Division-Into | 1981-10-22 | ||
EP84103637A Division EP0141009A3 (fr) | 1980-11-25 | 1981-10-22 | Segment d'analyse amovible pour rotor d'analyseur centrifuge |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0052770A1 true EP0052770A1 (fr) | 1982-06-02 |
EP0052770B1 EP0052770B1 (fr) | 1985-08-07 |
Family
ID=6117532
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP81108752A Expired EP0052770B1 (fr) | 1980-11-25 | 1981-10-22 | Rotor muni de segments amovibles pour analyseur centrifuge |
EP84103637A Withdrawn EP0141009A3 (fr) | 1980-11-25 | 1981-10-22 | Segment d'analyse amovible pour rotor d'analyseur centrifuge |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP84103637A Withdrawn EP0141009A3 (fr) | 1980-11-25 | 1981-10-22 | Segment d'analyse amovible pour rotor d'analyseur centrifuge |
Country Status (8)
Country | Link |
---|---|
US (2) | US4456581A (fr) |
EP (2) | EP0052770B1 (fr) |
JP (1) | JPS57156057A (fr) |
AT (1) | ATE14797T1 (fr) |
AU (1) | AU537606B2 (fr) |
CA (1) | CA1179867A (fr) |
DD (1) | DD202211A5 (fr) |
DE (2) | DE3044372A1 (fr) |
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- 1981-10-22 DE DE8181108752T patent/DE3171722D1/de not_active Expired
- 1981-10-22 EP EP84103637A patent/EP0141009A3/fr not_active Withdrawn
- 1981-10-22 AT AT81108752T patent/ATE14797T1/de not_active IP Right Cessation
- 1981-11-20 DD DD81235013A patent/DD202211A5/de unknown
- 1981-11-20 US US06/323,343 patent/US4456581A/en not_active Expired - Lifetime
- 1981-11-24 CA CA000390835A patent/CA1179867A/fr not_active Expired
- 1981-11-24 AU AU77808/81A patent/AU537606B2/en not_active Ceased
- 1981-11-25 JP JP56187906A patent/JPS57156057A/ja active Pending
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US4898832A (en) * | 1981-09-01 | 1990-02-06 | Boehringer Mannheim Gmbh | Process for carrying out analytical determinations and means for carrying out this process |
FR2537281A1 (fr) * | 1982-08-27 | 1984-06-08 | Elf Aquitaine | Rotor pour dispositif d'analyse a centrifugation |
EP0106398A2 (fr) * | 1982-10-20 | 1984-04-25 | Shell Internationale Researchmaatschappij B.V. | Analyseur centrifuge |
EP0106398B1 (fr) * | 1982-10-20 | 1988-05-25 | Shell Internationale Researchmaatschappij B.V. | Analyseur centrifuge |
EP0132510A3 (fr) * | 1983-04-25 | 1987-12-16 | Roche Diagnostics GmbH | Appareil d'analyse pour la détermination photométrique d'un paramètre d'un fluide |
EP0132510A2 (fr) * | 1983-04-25 | 1985-02-13 | Roche Diagnostics GmbH | Appareil d'analyse pour la détermination photométrique d'un paramètre d'un fluide |
FR2578054A1 (fr) * | 1985-02-28 | 1986-08-29 | Inovelf Sa | Procedes et dispositifs de preparation, conditionnement et utilisation de supports de reactifs |
US4756883A (en) * | 1986-09-16 | 1988-07-12 | E. I. Du Pont De Nemours And Company | Analysis device |
US4762683A (en) * | 1986-09-16 | 1988-08-09 | E. I. Du Pont De Nemours And Company | Analysis device |
FR2638844A1 (fr) * | 1988-11-09 | 1990-05-11 | Rene Hamelin | Dispositif a recipients multiples pour effectuer des tests, et element pour realiser un tel dispositif |
WO1990005294A1 (fr) * | 1988-11-09 | 1990-05-17 | Hamelin Rene | Dispositif a recipients multiples pour effectuer des tests, et element pour realiser un tel dispositif |
EP0417305A1 (fr) * | 1989-03-07 | 1991-03-20 | Idemitsu Petrochemical Co. Ltd. | Analyseur d'echantillon de liquide et procede d'analyse d'echantillon de liquide utilisant ledit analyseur |
EP0417305A4 (en) * | 1989-03-07 | 1992-04-22 | Idemitsu Petrochemical Co. Ltd. | Analyzer of liquid sample and analyzing method of liquid sample using said analyzer |
EP0428040A2 (fr) * | 1989-11-11 | 1991-05-22 | BEHRINGWERKE Aktiengesellschaft | Rotor à cuvettes |
EP0428040A3 (en) * | 1989-11-11 | 1992-01-02 | Behringwerke Aktiengesellschaft | Cuvette rotor |
US5186709A (en) * | 1989-11-11 | 1993-02-16 | Behringwerke Aktiengesellschaft | Cuvette rotor |
EP0628822A2 (fr) * | 1993-06-11 | 1994-12-14 | Ortho Diagnostic Systems, Inc. | Système automatisé d'analyse du sang |
EP0628822A3 (fr) * | 1993-06-11 | 1995-03-29 | Ortho Diagnostic Systems Inc | Système automatisé d'analyse du sang. |
US8301587B2 (en) | 2001-08-21 | 2012-10-30 | Hewlett-Packard Development Company, L.P. | Internet enabled computer system management |
Also Published As
Publication number | Publication date |
---|---|
US4814144A (en) | 1989-03-21 |
AU7780881A (en) | 1982-06-03 |
AU537606B2 (en) | 1984-07-05 |
EP0052770B1 (fr) | 1985-08-07 |
DD202211A5 (de) | 1983-08-31 |
EP0141009A2 (fr) | 1985-05-15 |
DE3171722D1 (en) | 1985-09-12 |
DE3044372A1 (de) | 1982-07-08 |
CA1179867A (fr) | 1984-12-27 |
ATE14797T1 (de) | 1985-08-15 |
US4456581A (en) | 1984-06-26 |
JPS57156057A (en) | 1982-09-27 |
EP0141009A3 (fr) | 1985-12-11 |
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